Abstract SY40-02: Identification of novel modulators of response to immune checkpoint blockade in lung cancer patients through the marrying of clinical and genomic data

2017 ◽  
Author(s):  
Phil Stephens
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Genomic Data ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Lung Cancer Patients

scholarly journals Proliferative potential and resistance to immune checkpoint blockade in lung cancer patients

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Sarabjot Pabla ◽  
Jeffrey M. Conroy ◽  
Mary K. Nesline ◽  
Sean T. Glenn ◽  
Antonios Papanicolau-Sengos ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Proliferative Potential ◽  
Lung Cancer Patients

Sequence of stereotactic ablative radiotherapy and immune checkpoint blockade in the treatment of metastatic lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20665-e20665 ◽  
Author(s):  
Ramya Pinnamaneni ◽  
Aparna Madhukeshwar Hegde ◽  
Sulochana Devi Cherukuri ◽  
Hyder Husain Arastu ◽  
Mark Bowling ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Synergistic Effects ◽  
Immune Checkpoint Blockade ◽  
Advanced Lung Cancer ◽  
Stereotactic Ablative Radiotherapy ◽  
Lung Cancer Patients ◽  
Immune Checkpoint Proteins

e20665 Background: Monoclonal antibodies targeting immune checkpoint proteins have recently been shown to elicit robust and durable responses in patients with advanced lung cancer. However, with response rates ranging from 15-20%, immunomodulatory strategies are needed to improve outcomes. Stereotactic ablative radiotherapy (SABR) may be a promising immunomodulatory strategy given its synergistic effects without added toxicity. Several pre-clinical trials combining SABR and immunotherapy have shown improvement in progression free and overall survival. Given this, it has been our multidisciplinary programmatic approach to bring in SABR in patients receiving immunotherapy for a potential immune boost. Methods: This is a retrospective study evaluating the overall survival (OS) of all lung cancer patients who received Nivolumab with SABR at our institution. We included lung cancer patients of all pathologic subtypes who received Nivolumab. We identified patients who received SABR, to sites of symptomatic metastatic disease, within 30 days preceding (Before) or during (Sandwich) Nivolumab treatment. Results: Out of 76 lung cancer patients treated with Nivolumab, 22 received RT- 10 Before and 12 Sandwich. At a median follow up time of 10.6 months (mo), median OS for patients with no RT was 4.8 mo, Before was 5.2 mo and Sandwich was not reached (NR) (p = 0.06). The 1 year OS for the Sandwich arm was 52.1%. When compared to no RT, the Before arm had a statistically insignificant reduction in mortality (HR 0.59, 95% CI 0.25 – 1.41, p = 0.24). The Sandwich arm had a statistically significant reduction in mortality (HR 0.37, 95% CI 0.14 – 0.94, p = 0.04). Conclusions: There is an improvement in OS when SABR is administered as a Sandwich approach during Nivolumab treatment, likely due to SABR-induced neoantigen release, increased PDL1 expression and subsequent abscopal effect. Further prospective studies are needed to evaluate optimal sequencing, dose and site of RT with immunotherapy. [Table: see text]

scholarly journals P09.09 Overall Survival in Elderly Metastatic Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Blockade

2021 ◽  
Vol 16 (3) ◽  
pp. S290
Author(s):  
M.F. Simões ◽  
M.F. Medeiros ◽  
D. Maciel Santana ◽  
C.I. De Andrade Souza ◽  
L.B. Mendes Gomes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients

scholarly journals Immune Checkpoint Blockade Enhances Immune Activity of Therapeutic Lung Cancer Vaccine

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 655
Author(s):  
Pournima Kadam ◽  
Ram P. Singh ◽  
Michael Davoodi ◽  
Jay M. Lee ◽  
Maie St. John ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Immune Checkpoint ◽  
Neutralizing Antibodies ◽  
Combined Therapy ◽  
Immune Checkpoint Blockade ◽  
Tumor Burden ◽  
Checkpoint Blockade ◽  
Lung Cancer Patients ◽  
Therapeutic Cancer Vaccines

Background: Immune checkpoint blockade that downregulates T cell evasion for effective immunity has provided a renewed interest in therapeutic cancer vaccines. Methods: Utilizing murine lung cancer models, we determined: tumor burden, TIL cytolysis, immunohistochemistry, flow cytometry, RNA Sequencing, CD4 T cells, CD8 T cells, CXCL9 chemokine, and CXCL10 chemokine neutralization to evaluate the efficacy of Programmed cell death protein 1 (PD-1) blockade combined with chemokine (C-C motif) ligand 21-dendritic cell tumor antigen (CCL21-DC tumor Ag) vaccine. Results: Anti-PD1 combined with CCL21-DC tumor Ag vaccine eradicated 75% of 12-day established tumors (150 mm3) that was enhanced to 90% by administering CCL21-DC tumor Ag vaccine prior to combined therapy. The effect of combined therapy was blocked by CD4, CD8, CXCL9, and CXCL10 neutralizing antibodies. Conclusion: PD-1 blockade therapy plus CCL21-DC tumor Ag vaccine could be beneficial to lung cancer patients.

scholarly journals The Prognosis and Immune Checkpoint Blockade Efficacy Prediction of Tumor-Infiltrating Immune Cells in Lung Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiangzheng Liu ◽  
Xueqian Shang ◽  
Jian Li ◽  
Shijie Zhang
Keyword(s):  
Lung Cancer ◽  
B Cell ◽  
Cancer Patients ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Enrichment Analysis ◽  
Immune Checkpoint Blockade ◽  
Hub Genes ◽  
Lung Cancer Patients ◽  
Kegg Pathways

BackgroundsThe high morbidity and mortality of lung cancer are serious public health problems. The prognosis of lung cancer and whether to apply immune checkpoint blockade (ICB) are currently urgent problems to be solved.MethodsUsing R software, we performed Kaplan–Meier (K-M) analysis, Cox regression analysis, functional enrichment analysis, Spearman correlation analysis, and the single-sample gene set enrichment analysis.ResultsOn the Tumor IMmune Estimation Resource (TIMER2.0) website, we calculated the abundance of tumor-infiltrating immune cells (TIICs) of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. B cell and myeloid dendritic cell (DC1) were independent prognostic factors for LUAD and LUSC patients, respectively. Enrichment analysis confirmed that genes highly related to B cell or DC1 were closely related to the immune activation of lung cancer patients. In terms of adaptive immune resistance markers, CD8A, CD8B, immunomodulators (immunostimulants, major histocompatibility complex, receptors, and chemokines), immune-related pathways, tumor microenvironment score, and TIICs, high B cell/DC1 infiltration tissue was inflamed and immune-activated and might benefit more from the ICB. Genes most related to B cell [CD19, toll-like receptor 10 (TLR10), and Fc receptor-like A (FCRLA)] and DC1 (ITGB2, LAPTM5, and SLC7A7) partially clarified the roles of B cell/DC1 in predicting ICB efficacy. Among the 186 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, there were three and four KEGG pathways, which partially explained the molecular mechanisms by which B cell and DC1 simultaneously predicted the prognosis and efficacy of immunotherapy, respectively. Among five immune subtypes, the abundance of B cell/DC1 and expression of six hub genes were higher in immune C2, C3, and C6.ConclusionB cell and DC1 could predict the prognosis and ICB efficacy of LUAD and LUSC patients, respectively. The six hub genes and seven KEGG pathways might be novel immunotherapy targets. Immune C2, C3, and C6 subtypes of lung cancer patients might benefit more from ICB therapy.

scholarly journals Clinical management of immune-related adverse events following immunotherapy treatment in patients with non-small cell lung cancer

2021 ◽  
pp. jim-2021-001806
Author(s):  
Hannah Elizabeth Green ◽  
Jorge Nieva
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Mechanism Of Action ◽  
Immune Checkpoint ◽  
Clinical Management ◽  
Immune Checkpoint Blockade ◽  
Small Cell ◽  
Checkpoint Blockade ◽  
Small Cell Lung ◽  
Autoimmune Conditions

The advent of checkpoint blockade-based immunotherapy is rapidly changing the management of lung cancer. Whereas past anticancer drugs’ primary toxicity was hematologic, the newer agents have primarily autoimmune toxicity. Thus, it is no longer enough for oncology practitioners to be skilled only in hematology. They must also understand management of autoimmune conditions, leveraging the skills of the rheumatologist, endocrinologist and gastroenterologist in the process. Herein we describe the mechanism of action and toxicities associated with immune checkpoint blockade in patients with lung cancer and provide a framework for management of adverse events.

scholarly journals Higher CD4/CD8 ratio of pleural effusion predicts better survival for lung cancer patients receiving immune checkpoint inhibitors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Po-Hsin Lee ◽  
Tsung-Ying Yang ◽  
Kun-Chieh Chen ◽  
Yen-Hsiang Huang ◽  
Jeng-Sen Tseng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pleural Effusion ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Lung Cancer Patients ◽  
Predicting Factor ◽  
Type 3

AbstractPleural effusion is a rare immune-related adverse event for lung cancer patients receiving immune checkpoint inhibitors (ICIs). We enrolled 281 lung cancer patients treated with ICIs and 17 were analyzed. We categorized the formation of pleural effusion into 3 patterns: type 1, rapid and massive; type 2, slow and indolent; and type 3, with disease progression. CD4/CD8 ratio of 1.93 was selected as the cutoff threshold to predict survival. Most patients of types 1 and 2 effusions possessed pleural effusion with CD4/CD8 ratios ≥ 1.93. The median OS time in type 1, 2, and 3 patients were not reached, 24.8, and 2.6 months, respectively. The median PFS time in type 1, 2, and 3 patients were 35.5, 30.2, and 1.4 months, respectively. The median OS for the group with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were not reached and 2.6 months. The median PFS of those with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were 18.4 and 1.2 months. In conclusion, patients with type 1 and 2 effusion patterns had better survival than those with type 3. Type 1 might be interpreted as pseudoprogression of malignant pleural effusion. CD4/CD8 ratio ≥ 1.93 in pleural effusion is a good predicting factor for PFS.

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